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M. L. De Rimini and G. Borrelli
a b
Fig. 9.1 (a) CARDIOGEN-82® system—cart containing generator and infusion system. (b) CARDIOGEN-82® sys-
tem—panel to edit elution and monitor infusion
use of the 82Sr/82Rb generator for as long as 4–5
weeks, after which the generator must be replaced.
The main physical characteristics of 82Rb are
reported in Table9.1, it decays into Krypton-82,
which is stable, by emitting a positron and a
neutrino.
Note
• Generator can be eluted every 7–10 min in
order to obtain the maximum performance
effectiveness. Consequently, the same time
(7–10 min) between two consecutive elutions
is the minimum time that must elapse between
the two phases of
82
Rb PET perfusion study:
basal and pharmacological stress test.
The 82Sr/82Rb radionuclide generator principle is based on inorganic cation exchange on
hydrous tin oxide (SnO2 × H2O, where × = 1, 2).
The target material is either 82RbCl or 82Rb metal.
Chemical processing of 82RbCl is faster, simpler,
and much safer than chemical processing of a
82
Rb metal target; therefore, the 82RbCl target
material is readily available at a high level of
purity. The Rubidium atom density is higher in
82
RbCl than in the pure metal, so the presence of
the chloride atom does not decrease yield compared with the pure metal. Moreover, target fabrication is simpler and safer with 82RbCl than
82
Rb metal. With both 82Rb metal and 82RbCl
with
targets, the buffered 82RbCl solution is ltered
and then transferred onto a column containing
equilibrated chelating cation exchange resin,
whereby the actual 82Sr/82Rb separation is
achieved: bivalent 82Sr2+ is chelated and retained
on the column at a high pH, while Rb + is eluted
and selected for automatica infusion into the
patient via an automatic injector system incorporated in the console of the Cardiogen system [6].
9.2.2 CardioGen-82® Quality Control
Procedures
The short physical half-life of 82Rb, 76 s, requires
that the steps for production and infusion occur
quite simultaneously via the closed and semiautomatic system which houses the 82Sr-85Sr/82Rb
generator. This is the reason why the system
should be placed near the patient positioned in
the PET machine.
In this system, Strontium-85 (85Sr) is the most
important contaminant in the production of 82Sr.
It has a longer half-life of 64.8 days. The ratio of
85
Sr to 82Sr must not exceed 5.0 for human use.
Because the characteristic gamma ray for 85Sr is
so close to the annihilation photon energy (514
versus 511 keV), care must be exercised in determining the amount of 85Sr contamination.
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Therefore, any procedure will be performed to
avoid unintended radiation exposure that occurs
when the 82Sr and 85Sr levels in 82RbCl injections
exceed the specied generator eluate limits, so targeted daily tests and procedures must be obtained
as generator eluate tests, before the patients studies, and aseptic techniques should be employed
throughout each procedure. The rst elution of the
day will prepare the generator column for use; this
will be a 50 mL elution. Daily procedures start to
carry out quality checks as indicated in the technical specications prepared by the manufacturer
and consist of three different phases summarized
in Table9.2 and briey commented below.
Table 9.2 CardioGen-82®—quality control (QC) proce-
dure steps (package insert and Rb-82 infusion system
user’s guide)
Washing Generator column wash
QC: Breakthrough
test
QC: Calibration
test
Measurement of Sr-82 and Sr-85
content in the eluate
Compares the infusion system
assay of the eluate to a dose
calibrator assay of the eluate
• Washing: This rst phase is only for washing
the lines belonging to the whole system.
The washing phase is followed by a second
elution and the carrying out of two quality
controls:
1. The breakthrough test is needed for verifying
radionuclide purity. It allows to determine the
amount of 82Sr and 85Sr present as impurities
in the sample solution of the eluate. The
results of these tests are valued at 60min post
the end of elution and affect the feasibility of
the study (Fig.9.2). With this aim, it is man-
datory that the following values are carefully
veried:
(a) 82Sr content must not be more than 0.02
uCi/mCi of 82Rb.
(b) 85Sr content must not be more than 0.2
uCi/mCi of 82Rb.
2. The calibration test, which allows to calibrate
the system in order to work at a constant dose
for the entire session.
Fig. 9.2 Quality control phases: daily worksheet for the
breakthrough test. It controls for radionuclide purity,
allows to determine the amount of
82
Sr and 85Sr present as
impurities in the sample solution of the eluate. The results
of this test are valued at 60min post the end of elution and
they condition the feasibility of the study
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M. L. De Rimini and G. Borrelli
Table 9.3
(can be modied relatively to the PET scanner)
Mode switch Automatic infusion
Elution volume 99 mL
Patient volume 50 mL
Patient dose 40–60 mCi
Elution volume 99 mL
Elution: manual setting general parameters
The different elutions and administrations of
the dose to the patient are managed by an electronic panel (Fig. 9.1b). This system interface
allows to set the elution volumes, the activities
(according to ALARA principles), and the volume for each dose to be administered to the
patient as well as the speed and the type of infusion (Table9.3). It is well known that the use of
automatic injectors will facilitate uniform delivery of the radiotracer and standardize the input
function for MBF quantitation; therefore, this
infuser system connected to the 82Rb generator
can be considered an advantage in the determination of MBF [7].
The system is semiautomatic and some settings, as the waste management, loading of raw
materials, etc., are manually edited by the operator and are justied by usage over time.
It is mandatory to stop the use of the generator
at indicated expiration limit.
9.3 82Rb-PET/CT: Protocols
The short physical half-life of 82Rb allows for an
efcient fast protocol, approximately 35–45min
for both baseline and pharmacological stressor
phases. It must be underlined that the time for
each scan is linked to the physical half-life of the
tracer used, respectively: 7–8 min for 82Rb,
20min for 13N-NH3.
Due to the short physical half-life of tracer, an
exercise test cannot be associated, so all stress
studies are performed with pharmacologic
stressor, dobutamine, or vasodilators, with the
following features: adenosine receptors as dipyridamole, adenosine, or regadenoson, more selectively A2a receptors [3]. Theoretically, vasodilator
stressor tests are preferred considering that 82Rb
acts as a potassium analogous, allowing a high
extraction fraction at high ow rates.
Note
1. Myocardial
82
Rb-PET/CT: Patient
preparation
(a) The preparation of patient ongoing to
myocardial 82Rb-PET/CT is substantially
similar to that of routine
99m
Tc SPECT
MPI one.
(b) Fast is needed for a minimum of 4 h prior
to the scheduled study time. A large stomach volume, in fact, has been found associated with more severe MPI interference,
suggesting that sufcient fasting prior to
imminent 82Rb PET may be important to
reduce aspecic interference from adjacent radiotracer activity and consequently
improve the interpretation of MPI results
especially in small patients [8].
(c) Avoid smoking for at least 4 h and avoid
caffeine intake for at least 24 h before
vasodilator stress.
2. Myocardial 82Rb-PET/CT: Pharmacological
stressors
(a) Vasodilator stress is chosen in the aim to
provide maximal hyperemia. The vasodilator hyperemic stimulus activates specic purinergic receptors on coronary
resistive vessels, thereby increasing MBF
by direct vasodilation. It can be obtained,
respectively, by the use of:
Adenosine (140 mg/kg/min. i.v. over
4–6 min), dipyridamole (0.56 mg/kg
intravenous infusion over 4 min), or
regadenoson (0.4 mg rapid intravenous bolus over 10 s) which are regularly used as stressor for
82
Rb PET
stress scan.
Among these, regadenoson has been
reported as particularly idoneous for
82
Rb in terms of strict concordance
between stressor and tracer, respectively, related to a rapid pharmacological action and a rapid acquisition scan,
due to the kinetics and short half-life
of 82Rb [3]. After excluding contrain-
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dications, the stress agent can be
infused on the basis of standard protocols for each stressor agent.
(b) Dobutamine (stepwise increase in infu-
sion from 5 or 10 μg/kg/min up to 40 μg/
kg/min to achieve >85% predicted heart
rate) or dobutamine plus atropine stress
(atropine boluses may be used to augment
heart rate response). Dobutamine, more
frequently associated with echocardiographic technique for myocardial viability assessment, is a sympathomimetic
amine that acts through α and β adrenoceptors stimulating both positive inotropic and chronotropic effects and
enhancing MBF, mainly through metabolic vasodilatation. In addition, dobutamine increases MBF through direct β2
adrenoceptor-mediated vasodilatation of
coronary resistive vessels. It can be associated with 82Rb PET as an alternative to
the previously mentioned group of stressors in fact, although vasodilator agents
such as adenosine may be more efcient
stressors, dobutamine offers a more physiological approach to assess the demand
of ischemia [9].
Today PET scanners let to obtain good quality
images. Acquisition and reconstruction parameters can vary between different scanners. The use
of 3D PET/CT scanners and upgraded software
can allow to inject half activity of
82
Rb with a preserved image quality and reduced dose effective
to the patient.
For the analysis, the quantication of MBF is
the prevalent focus of the study. It requires accurate measurement of the total tracer activity
transported by the arterial blood and delivered to
the myocardium over time. Some standardization
of image acquisition and reconstruction protocols
for accurate MBF quantication has been suggested, but it is not universally applied.
In practice, for all data available from a PET
myocardial perfusion study, it is recommended:
list-mode acquisition because it allows exibility in
the timing and reconstruction of dynamic images
for MBF.The list-mode is the ideal approach for
the capability to acquire all the sequences (multiframe, ECG-gated) and allows the reconstruction
from the whole set of images or selected portion of
it. PET MPI enables perfusion study images, allowing measurements of LV volumes and ejection
fraction, thanks to ECG-gated images, and with
dynamic images for MBF quantication, by using
also a retrospective selection of the onset of the
myocardial phase, which can be delayed in low
cardiac output conditions or poor bolus quality.
82
Due to the short half-life of
Rb, both sets of
images, basal and stress scans, can be acquired
using the same sized dose.
A post-stress CT can be also developed for
photonic attenuation correction (AC-CT), and to
avoid motion artifacts due to the patient movement during stressor test or due to changes of the
VS silhouette for transient dilation based on ischemic LV dysfunction.
Low-dose (LD) CT, nondiagnostic but useful
for photonic attenuation correction (AC-CT), is
generally associated with co-registration. The
acquisition parameters vary with the conguration of the CT scanner and the number of detectors; however, the settings of an ungated scan,
commonly used, include slow rotation speed,
high-potential tube, and low amperage. An ECGgated CT scan perspective for AC and calcium
score evaluation can be preferably performed in
inspiratory apnea and higher amperage, in which
the X-ray input is active only in the diastolic
phase of the cardiac cycle, typically 75–80% of
the RR. This approach, compared to a gatedscan, increases the dosimetric load to the patient
and can translate into more misalignment of CT
and PET images (apnea vs. free breathing).
Therefore, it is always indispensable to verify the
consistency of alignment of the images and use a
dedicated software for the realignment of the two
data series. In selected patients, it is also possible
to combine a diagnostic CT coronary angiography for the evaluation of the coronary lumen.
An example of a dynamic acquisition protocol
is reported in Fig.9.3. It has been selected for a
PET/CT tomograph system, 3D, lutetium oxyorthosilicate (LSO) crystals 13 × 13 × 20 [10].
Typically, basal conditions PET scan is followed by stress imaging on the same day sequence.
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M. L. De Rimini and G. Borrelli
Fig. 9.3 82Rb PET/CT MPI scan protocol, 7 min/each phase, dynamic list mode acquisition. Proposal used on PET/CT
tomograph system, 3D, lutetium oxyorthosilicate (LSO) crystals 13 × 13 × 20
An inverse protocol (stress-rst) or stress-only
imaging is feasible but not recommended in the
routine practice for a quantitative PET.
The acquisition steps in Fig.9.3 are sequen-
tially summarized below:
particularly during regadenoson stress test,
leading to a misalignment of the drawn myo-
cardium contour which affects the evaluation
of activity in the heart with increased activity
in the RCA territory and decreased values in
the LAD one’s, resulting in unrealistic high
•
CT scout followed by LD AC-CT
• Rest scan: 82Rb infusion, activity: 40–50 mCi;
MPI rest scan, 7 min, dynamic list mode gated
rest acquisition
• Stressor pharmacological test
MBF values (5 mL/min/g). Proper alignment
of the automatically drawn myocardium contours must be obtained for obtaining a correct
PET quantitative measure, which decreased
after correction to realistic values [
11].
• At peak stress: 82Rb infusion, activity 40–50
mCi, followed with dynamic list mode acquisition gated stress scan, 7min
Note
9.4 82Rb-PET/CT MBF–MFR
Filtered backprojection with a reconstruction lter and measured AC produces the best myocar-
• Focused attention should be paid to the detection and correction of myocardial creep, a
technical problem occurring in more than half
of the patients during stressor 82Rb PET and
dial image uniformity, but specic reconstruction
details should be checked for each scanner. The
PET reconstruction with iterative methods, in
contrast to the ltered backprojection in SPECT,
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protects from artifacts by subdiaphragmatic high
activity, avoiding subtraction of counts in the
inferior wall of the LV.Other artifacts should be
carefully considered for the PET perfusion scan
(without MBF), typically the acquisition still earlier, before the complete clearance of the radiopharmaceutical from the blood pool, adversely
affecting the quality of perfusion images, so in
healthy subjects it is necessary to start perfusion
phase at: 180–240 s for 13N-NH3 and 90–120 s
for 82Rb.
Note
(a) On the reconstructed images, it is mandatory
to control the perfect overlapping of CT and
PET LV silhouettes for each phase of scans
and proceed with images motion correction
if necessary. Today, most of the PET/CT systems include dedicated software to correct
the misalignment transmission-emission, by
operating correction of the sinogram and
subsequent reconstruction with proper attenuation map.
(b) PET reconstructed images, gated and
ungated, can be displayed using any of the
software packages developed for SPECT and
adapted for PET.
which describes a mono-compartmental model
82
preferably used for
Rb.
Today software for quantization of MBF and
myocardial ow reserve (MFR) are available in a
user-friendly way. Dynamic acquisition is necessary from the beginning, at the time of tracer
injection, to be continued until the tracer uptake
in the myocardium is completed. Volumes of
interest are obtained on the myocardial ventricular cavities, where the activity input is taken on a
ROI positioned on LV blood pool [15] and the LV
wall is then identied. Time/activity curves are
then tted and the related parameters are calculated to obtain, respectively, the tracer input function and the tracer amount within the myocardium.
According to the chosen compartmental model,
these values are included in the equations for the
calculation of the kinetic parameter that best represents MBF. To ensure accurate estimates of
MBF and MFR, it is critical to verify that each
dynamic series is acquired and analyzed correctly, with thorough review of quality assurance
information including orientation of LV long
axis, sampling of myocardium and arterial blood
regions, motion detection, dynamic time-activity
curves, and kinetic modeling curve-t [16].
Note for MBF Evaluation
The largest experience in cardiac quantitative
PET is in the measurement of MBF.To estimate
MBF, time-activity curves are obtained from
dynamic PET images acquisition. Curves are
then t to a mathematic model describing the
tracer kinetics over time. Various compartmental
models have been proposed for the measurement
and many studies have compared their reliability
and methodological inequalities that must be
considered if the results of diverse laboratories
have to be compared.
The two models most commonly used for
82
Rb and 13N-ammonia are the one-tissuecompartment model [12] and the simplied
retention model [13].
The technical details of these techniques go
beyond the aim of this chapter, but it could be
useful to underline, among these, the algorithm
proposed by Lortie for MBF evaluation [14]
(a) Accurate and reproducible quantication of
MBF is possible with both 13N-ammonia and
82
Rb (both of which are Food and Drug
Administration approved).
(b) Consistent tracer injection proles improve
the reproducibility of MBF measurements.
(c) The administered dose must be adjusted to
avoid detector saturation during the blood
pool phase, which can be particularly challenging with 82Rb.
(d) List-mode acquisition enables reconstruction
of static, gated, and dynamic datasets. Dynamic
datasets are used for blood ow quantication
with compartmental modeling [7].
MFR is calculated by the MBF report after
baseline and hyperemic stimulus usually induced
with dipyridamole, adenosine, or regadenoson. It
may be useful to remember that PET technique
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M. L. De Rimini and G. Borrelli
does not measure volume of blood ow in the
epicardial coronary arteries directly but rather
blood ow in myocardial tissue. Thus, the term
MFR is more appropriate in respect of the largely
used denition “coronary ow reserve” (CFR)
invasively determined. The standard units of
MBF are commonly expressed as mL/min/g.
Hyperemic MBF and MFR provide useful
information on coronary vasodilator ow capacity and characterization of ow-limiting
CAD.Both parameters also share the same limitation for differentiating predominant focal
obstructive stenosis from diffuse atherosclerosis
and microvascular dysfunction. In 8 studies consisting of 382 healthy subjects, MBF -MFR value
using 82Rb PET has been evaluated as a weighted
mean of:
• Resting MBF: 0.74 mL/g/min (range,
0.69–1.15)
• Stress MBF: 2.86 mL/g/min (range, 2.5–3.82)
• MFR: 4.07 (range, 3.88–4.47) [7]
The young population, or healthy volunteers,
or men without coronary risk factors, can limit
the overlap of these results in the real life. In an
older population with a possible burden of coronary risk factors in fact, it is possible to obtain
values below these ranges without any evidence
of obstructive epicardial CAD, often due to the
effects of diffuse CAD and microvascular
disease.
So, while hyperemic MBF and MFR provide
useful information on coronary vasodilator ow
capacity and characterization of ow-limiting
CAD, both of them got the same limit in differentiating predominant focal obstructive stenosis
from diffuse atherosclerosis and microvascular
dysfunction.
Anyway, for a better understanding of this
important tool at our disposal with quantitative
PET, we must always keep in mind that in humans
resting MBF remains relatively preserved across
a wide range of coronary stenosis severity, thanks
to the gradual autoregulatory vasodilation of
resistive vessels to maintain resting myocardial
perfusion in the setting of upstream stenosis.
Conversely, resting MBF falls only in case of
critical subocclusive stenosis with poorly developed collateral blood ow.
Hyperemic MBF and MFR are relatively preserved for coronary lesions with less than 70%
angiographic stenosis or with preserved fractional ow reserve and consistently reduced in
lesions with greater than 70% luminal narrowing
or those with abnormal FFR.
Hyperemic MBF and MFR can provide useful
information on coronary vasodilator ow capacity, addressing the characterization of owlimiting CAD, but they are not able to distinguish
the dominant focal obstructive stenosis from diffuse atherosclerosis and microvascular dysfunction. With this aim, invasive coronary angiography
(ICA) or coronary CT angiography (CCTA) can
differentiate the different categories of patients
[17]. For most patients, hyperemic MBF and
MFR are concordant both in terms of normal or
abnormal responses [18]; however, discordance
can be observed in a minority of patients showing
abnormalities of MBF, considering that MFR is a
ratio between hyperemic and resting
MBF. Among the patients mentioned above,
showing discordant ndings of MBF and MFR,
we report, for example, those one with prior
myocardial infarction who may show relatively
preserved MFR in infarct-related territories
because of low resting MBF.
Coronary stenosis of intermediate severity is
associated with signicant variability in hyperemic MBF and MFR at PET, whereas their gradual reductions can be due to a progressive loss in
maximum vasodilator capacity with increasing
stenosis severity, modulated by different agents
such as coronary resistance, development of collateral blood ow, diffuse coronary atherosclerosis, and microvascular dysfunction.
Exceptions to this gradual response are some
higher-risk subgroups of patients affected with
diabetes, other cardiovascular risk factors, and
chronic kidney disease where both MBF and
MFR can appear reduced even in the absence of
overt obstructive stenosis.
These patients show high-risk CAD and CAD
complications even in case of relatively low-risk
at MPI ndings. This poor prognosis is probably
due to increased rates of diffuse epicardial CAD
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and microvascular disease, leading to improved
performance of quantitative PET compared with
relative SPECT MPI [19].
Note
Modied from joint position paper of the SNMMI
cardiovascular council and the ASNC [7].
(a) Preserved stress MBF >2 mL/min/g and
MFR >2 can exclude the presence of highrisk angiographic disease (negative predictive value 95%).
(b) A severely decreased global MFR (<1.5 mL/
min/g) can correlate with adverse cardiac
events but the likelihood of multivessel
obstructive disease diagnosis requires more
studies including ECG, evaluation of LV
contractile function and volumes, ICA, or
CCTA.
(c) Both regional decreases in stress MBF (<1.5
mL/min/g) and MFR (<1.5) in a vascular territory may indicate regional ow-limiting
disease.
bility, or better capability, of assessing MBF.It is
a particularly powerful tool for patient outcome,
as it reects the end result of many processes that
lead to atherosclerosis.
Multimodal scanners, combining PET and
SPECT with high-resolution multidetector CT,
are currently available and offer the ability to
assess functional evaluation of transient ischemia
or viability associated with LV function and
crossed with the anatomy. A systematic review
and meta-analysis are aimed to assess the diagnostic accuracy of 82Rb PET in patients with
known or suspected obstructive CAD in comparison with the reference standard ICA and with
contemporary SPECT technology utilizing ECGgating and AC methods. In the review, including,
respectively, 1344 PET and 1755 SPECT patients,
82
Rb PET showed sensitivity 90% and specicity
88% in detection of obstructive CAD vs.
ICA. Moreover, 82Rb PET showed better accuracy, despite advances in SPECT technology
consisting of ECG-gating and AC-CT, and
remains superior than SPECT in the workup of
patients with CAD [22].
9.5 82Rb PET MPI Versus
SPECTMPI
MPI, both PET and SPECT, is highly accurate in
detection and risk stratication of CAD, guiding
patient outcome and workup. PET and PET/CT
seem to be more accurate than SPECT in the
diagnosis of obstructive CAD, especially among
patients undergoing pharmacological stress.
The high specicity and overall diagnostic
accuracy of
SPECT reduce the number of false positives even
more among women and over-weight patients.
Bateman [20] demonstrated that PET MPI is
superior to SPECT in quality image, interpretative certainty, sensibility, specicity, and diagnostic accuracy both in men and women, in obese
and nonobese patients, and for correct identication of multivessel coronary disease (MVD).
Same results have also been reported independently of the coronary lumen stenosis (≤50% and
≥70% coronary stenoses) [21]. So, the additional
value of PET consists predominantly in the capa-
82
Rb Gated-PET/CT vs. gated-
9.6 Clinical Applications
Note A sequence of detailed clinical cases are
attached in the appendix to this paragraph, in
order to highlight some of the aspects frequently
reported in the diagnostic use of 82Rb PET/CT
MPI. The clinical cases will be indicated in
numerical sequence in the text, each of them
within its own specic clinical context and
reported by a brief comment, in order to emphasize the clinical impact of the corresponding
information obtained from imaging.
In the past, PET signicantly contributed to
improve the knowledge of cardiac physiology
and to better understand some physiological processes by quantication invivo. Nevertheless, its
clinical applications in cardiac disease were limited, due to high cost and reduced availability of
machines and tracer suitable.
In the recent years, PET has reached growing
role and now it is widely used in patients with
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M. L. De Rimini and G. Borrelli
known or suspected CAD and/or dysfunctionally
LV, showing high sensibility (93%) and specicity (92%) in hemodynamically signicant stenosis at ICA.It can be due to:
• Tracer availability, thanks to 82Rb for the feasibility of on-site generator for clinical utilization in those structures without a cyclotron.
• The optimal intrinsic characteristics of PET,
in terms of spatial and temporal resolution, the
latter allowing MBF evaluation.
• The implementation of multimodality technique with hybrid machines.
Although it has been consistently demon-
strated the improved diagnostic sensitivity for
CAD of PET MBF and MFR evaluation, a
potential reduction in the specicity of stress
MBF and MFR measurements can be found due
to the possible interference on it of diffuse atherosclerosis or microvascular disease processes
[23, 24].
This approach may prove useful information
in case of MVD, as observed in the Clinical Case
Number 1.
Clinical Case No. 1: The spontaneous con-
•
trast of metallic stent at PET/CT fusion images
let better recognize the correct pertinence of
ischemia territory between multiple stenting
vessels.
One of the most common additional data of
MPI with multimodal technique is the evidence
of calcied plaques along the coronary branch
path. It is simply evident by spontaneous contrast
in co-registration CT or, even better, assessable in
terms of calcium score when the CT is conducted
with a target gated technique. It has been reported
the prognostic value of calcic atheromasia on
the main epicardial coronary artery and even better of the evaluation of coronary artery calcium
score (CACS), whereas high score can inuence
the prognosis of patients both in case of transient
ischemia or preserved perfusion at MPI.
9.6.1 Multimodality Technique
PET/CT
On this specic need, the added value of multimodality technique with hybrid machines,
equipped with superior AC abilities, has allowed
higher accuracy of 82Rb PET MPI-CT in diagnostic efcacy of CAD. It has been demonstrated
that the fusion imaging (PET/CT) will optimize
precisely ischemic pertaining of the affected vessel, even when ischemia is due to multiple vessels. It allows a stronger clinical impact of
PET/CT in suggesting targeted coronary arteries
revascularizations and can optimize the diagnostic performance of technique, more helpful in
RCA and LCX territories, showing that MPI
PET/CT “is not only nice to have, but truly
needed.” Similarly, considering the intrinsic
metallic contrast of stenting vessels on CT, the
multimodal fusion images can help to match the
perfusion map in specic pertaining to the stenting vessel.
82
Rb
• Clinical Case Nos. 2 and 3 underline the
approach of a combined analysis of 82 Rb PET/
CT MPI and calcium score.
Evidence of calcic deposit on coronary main
vessels is becoming relatively frequent evidence
in multimodality studies of MPI/CT.
It does not imply necessarily functional
matching with ischemia, but the increase in
CACS can affect the long-term prognosis with a
stronger value when it is associated with perfusion defects. Calcium scoring has been studied
extensively over the past decade for predicting
outcome in generally asymptomatic subjects at
intermediate clinical risk for CAD.
In this purpose, Chang [
25] in a large popula-
tion consisting of 1126 generally asymptomatic
subjects without previous cardiovascular disease,
who underwent multimodality MPI techniques,
demonstrated that CACS may better estimate
longer-term prognosis because of its ability to
detect varying degrees of coronary atherosclero-
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sis before the development of stress-induced
myocardial ischemia. They showed that CACS
and MPI ndings are independent and complementary predictors of short- and long-term cardiac events, whereas, despite a normal MPI
result, a severe CACS identies subjects at high
long-term cardiac risk.
On this basis, the AA support the utility of
performing a CACS evaluation in patients at
intermediate or high clinical risk for CAD also
after a normal perfusion result, to better stratify
those who will have a high long-term risk for
adverse cardiac events.
On the same aim, quantitative analysis integrating per-vessel ischemic total perfusion decit, hyperemic MBF and CFR with CACS,
improves the accuracy of 82Rb PET/CT myocardial perfusion imaging for regional prediction of
CAD. The combined use of CACS, perfusion
data, and quantitative coronary vascular function
may predict more accurately the presence of
obstructive CAD [26].
9.6.2 82Rb PET/CT inObstructive
andNonobstructive CAD
The European Society of Cardiology guidelines
on myocardial revascularization and management of stable CAD, from 2014 and 2013, stress
the role of noninvasive testing including cardiac
PET in patients with suspected CAD as follows:
after initial pre-testing of CAD likelihood,
patients with an intermediate risk of signicant
CAD are advised to undergo functional testing or
CTA, with the purpose of distinguishing between
obstructive and nonobstructive CAD.PET is one
of the imaging modalities recommended for this
purpose.
Thanks to the good quality of images, the
diagnostic accuracy over the traditional MPI, and
the feasibility of on-site generator for clinical utilization,
clinically detection of CAD in subjects at intermediate pretest likelihood and suitable for pharmacological stressor [27].
82
Rb has been widely used to facilitate
Still more specic indications, among these
group of subjects, are in the obese ones, where
the PET AC-CT allows to avoid artifacts, with
drastic advantage of diagnostic information, and
once again in women, considering the dosimetric
82
advantage of
Rb PET.
Semiquantitative analysis for MPI has become
a major part of nuclear cardiology practice.
Current PET software tools are specically
upgraded for 82Rb database and can automatically quantify myocardial function and perfusion
maps, by estimating summed perfusion scores,
total perfusion defect, overall defect extension,
systolic and diastolic functionally data, allowing
high diagnostic accuracy for detecting CAD and
predict outcomes [28]. An extension of perfusion
defect ≥10% of LV is a poor prognostic factor, it
can predict the need and benet of revascularization and can inuence the workup of patients
with strong clinical impact in guiding the need of
revascularization rather than medical treatment.
It is crucial to dene the functional signicance
of a stenosis with MPI, to successfully establish
the workup of the patient [29], considering that
not all stenoses can induce the same functional
signicance in terms of transient ischemia as
well as in terms of risk. It has been demonstrated,
in fact, that the severity of coronary stenosis at
angiographic lm is a bland predictor of the relevance of the stenosis itself and that the same
percentage of vessel stenosis can induce different
pathophysiological effects, varying for each
patient. The FAME trial, by using the fractional
ow reserve (FFR) as cutoff value for myocardial
ischemia versus functional severity of coronary
artery stenoses, demonstrated that not all coronary stenosis are ow limiting and that severe
stenoses by ICA can have completely different
functional importance at FFR [
30]. Conversly, it
has been well demonstrated that 35% of categories of stenosis ranging between 50 and 70% can
induce ischemia.
At the same time though, it has been demonstrated that invasive procedures such as ICA, coronary artery bypass grafting (CABG), and
percutaneous transcoronary intervention (PTCI)
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